Comprehensive survey and geometric classification of base triples in RNA structures

Almakarem, Amal S Abu; Petrov, Anton I.; Stombaugh, Jesse; Zirbel, Craig L.; Leontis, Neocles B.

doi:10.1093/nar/gkr810

Cited by 91 publications

(97 citation statements)

References 43 publications

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“…These new RNA switches are smaller than previously discovered "riboswitches" and may be the simplest form of ligand-responsive mechanical modules in nucleic acids. observed for G-C pairs interacting with arginine in protein-RNA complexes (24,25) and with guanosine in C-G ○ G triples (26,27) ( Fig. 2A).…”

Section: Resultsmentioning

confidence: 84%

“…Structural comparison shows that the guanine base may engage in similar interactions with subdomain IIa as those observed for benzimidazole inhibitors. The resulting arrangement corresponds to the interaction of guanosine with a Watson-Crick G-C pair in a geometry that accounts for one of the most frequently occurring base triples in RNA folds (27).…”

Section: Discussionmentioning

confidence: 99%

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Functional conservation despite structural divergence in ligand-responsive RNA switches

Boerneke¹,

Dibrov²,

Gu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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An internal ribosome entry site (IRES) initiates protein synthesis in RNA viruses, including the hepatitis C virus (HCV). We have discovered ligand-responsive conformational switches in viral IRES elements. Modular RNA motifs of greatly distinct sequence and local secondary structure have been found to serve as functionally conserved switches involved in viral IRES-driven translation and may be captured by identical cognate ligands. The RNA motifs described here constitute a new paradigm for ligandcaptured switches that differ from metabolite-sensing riboswitches with regard to their small size, as well as the intrinsic stability and structural definition of the constitutive conformational states. These viral RNA modules represent the simplest form of ligand-responsive mechanical switches in nucleic acids.

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Section: Resultsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Functional conservation despite structural divergence in ligand-responsive RNA switches

Boerneke¹,

Dibrov²,

Gu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…We attempted to model this base triple interaction based on the following facts: (i) loop 1 interacts with the major groove face of stem 3 and forms base triple(s) as in other pseudoknots. (ii) The third base in this base triple interaction can be A, C, or U but not G. Six base triple families whose third nucleotide interacts with the major groove face of a Watson-Crick base pair were identified via the RNA base triples database (http://rna.bgsu.edu/triples/triples .php) (53). Among them, the cWW_tHS GCA (Leontis-Westhof nomenclature [54]) base triple (Fig.…”

Section: Discussionmentioning

confidence: 99%

Novel cis -Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

Liu

Jiang

et al. 2013

J Virol

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c cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5= cyclization sequence (5=CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5=CS, and the presence of DCS-PK facilitates the formation of 5=-3= RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution. T he flavivirus genus contains numerous important agents of human infectious diseases, including dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), and tick-borne encephalitis virus (TBEV). Human infection by flaviviruses can result in symptoms ranging from mild fever to severe encephalitis and hemorrhagic fever. Due to lack of effective vaccines and specific medicines against many flaviviruses, they pose a significant threat to human health around the world.Flaviviruses are enveloped RNA viruses with single-stranded, positive-sense genomes. Their 5= capped viral genome RNA (vRNA) is approximately 10 to 11 kb and contains a single open reading frame (ORF) flanked by 5= and 3= untranslated regions (UTRs). The ORF encodes a polyprotein with more than 3,000 residues, which is cotranslationally and/or posttranslationally proteolytically processed into three structural proteins (capsid, pre-membrane/membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) by viral and cellular proteases. NS3 and NS5 perform essential enzyme activities required for vRNA replication. The C-terminal domain of NS3 has helicase/NTPase (1) and RNA triphosphatase activities (2, 3). The N-terminal domain of NS5 encodes guanylyltransferase (4) and methyltransferase activities (5, 6), whereas the C-terminal domain of NS5 has RNA-dependent RNA polymerase (RdRp) activity. These enzyme activities are involved in vRNA synthesis, 5= capping, and internal adenosine methylation (7).The 5=UTR, 3=UTR, and capsid-coding sequence are involved in vRNA replication, translation, and perhaps encapsidation, and many cis-acting elements have ...

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“…G20 interacts with the minor-groove edge of the base pair via its Hoogsteen face to form a rare C:G:G cWW/tSH cis WatsonWatson/trans Sugar-Hoogsteen (cWW/tSH) triplex, which has been observed only once before, in the E. coli 16S rRNA (22,23). Triplexes 2 and 3 are conserved between ToxI Bt and ToxI Pa , and both are common RNA tertiary motifs.…”

mentioning

confidence: 99%

Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot

Short

Pei

Blower

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Bacterial small RNAs perform numerous regulatory roles, including acting as antitoxic components in toxin-antitoxin systems. In type III toxin-antitoxin systems, small processed RNAs directly antagonize their toxin protein partners, and in the systems characterized the toxin and antitoxin components together form a trimeric assembly. In the present study, we sought to define how the RNA antitoxin, ToxI, inhibits its potentially lethal protein partner, ToxN. We show through cross-inhibition experiments with the ToxIN systems from Pectobacterium atrosepticum (ToxIN Pa ) and Bacillus thuringiensis (ToxIN Bt ) that ToxI RNAs are highly selective enzyme inhibitors. Both systems have an "addictive" plasmid maintenance phenotype. We demonstrate that ToxI Pa can inhibit ToxN Pa in vitro both in its processed form and as a repetitive precursor RNA, and this inhibition is linked to the self-assembly of the trimeric complex. Inhibition and self-assembly are both mediated entirely by the ToxI Pa RNA, with no requirement for cellular factors or exogenous energy. Finally, we explain the origins of ToxI antitoxin selectivity through our crystal structure of the ToxIN Bt complex. Our results show how a processed RNA pseudoknot can inhibit a deleterious protein with exquisite molecular specificity and how these self-contained and addictive RNA-protein pairs can confer different adaptive benefits in their bacterial hosts.RNA inhibition | mRNA interferase | RNA-protein complex | abortive infection | plasmid stabilization

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Comprehensive survey and geometric classification of base triples in RNA structures

Cited by 91 publications

References 43 publications

Functional conservation despite structural divergence in ligand-responsive RNA switches

Functional conservation despite structural divergence in ligand-responsive RNA switches

Novel cis -Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot

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